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Compound Detail

CHEMBL3989870

BERZOSERTIB
🧪 Phase II
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🧪 Phase II
CNCc1ccc(-c2cc(-c3nc(-c4ccc(S(=O)(=O)C(C)C)cc4)cnc3N)on2)cc1

Basic Information

ChEMBL ID CHEMBL3989870
Name BERZOSERTIB
Phase Phase II
Structure Type MOL
InChI Key JZCWLJDSIRUGIN-UHFFFAOYSA-N

Known Names

Berzosertib M-6620 M6620 VE-822 Vx-970 VX970
22
Targets
40
Activities
2
Assay Types
2
PK Parameters
20
Publications
6
Known Names
18
Indications
1
Mechanisms

Molecular Properties

463.6
MW (Da)
3.95
ALogP
8
HBA
2
HBD
124.0
PSA (Ų)
0.42
QED
0
Ro5 Violations
7
Rot. Bonds

Drug Information

Molecule Type Small molecule
Chirality Achiral

Flags

Natural Product
USAN Stem -sertib
USAN Year 2016

Extended Properties

Molecular Formula C24H25N5O3S
MW 463.56
Aromatic Rings 4
Heavy Atoms 33
NP-Likeness -1.01

Mechanism of Action

Mechanism Action Type Target Direct Efficacy
Serine-protein kinase ATR inhibitor INHIBITOR Serine/threonine-protein kinase ATR

Indications

Leiomyosarcoma Ovarian Neoplasms Ovarian Neoplasms Ovarian Neoplasms Prostatic Neoplasms Prostatic Neoplasms Small Cell Lung Carcinoma Carcinoma, Non-Small-Cell Lung Carcinoma, Squamous Cell Colorectal Neoplasms Head and Neck Neoplasms Neoplasms Pancreatic Neoplasms Squamous Cell Carcinoma of Head and Neck Squamous Cell Carcinoma of Head and Neck Squamous Cell Carcinoma of Head and Neck Triple Negative Breast Neoplasms Uterine Cervical Neoplasms

Activity Summary

IC50 20 meas. best 9.77
Ki 20 meas. best 9.83

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Serine/threonine-protein kinase ATR
CHEMBL5024
Ki 9.83 9.768 0.1 5
Serine/threonine-protein kinase ATR
CHEMBL5024
IC50 9.77 8.035 0.2 6
Alpha-1-antitrypsin-related protein
CHEMBL4879431
IC50 9.7 9.7 0.2 1
SARS-CoV-2
CHEMBL4303835
IC50 8.37 6.4633 4.3 6
Unchecked
CHEMBL612545
IC50 8.3 8.3 5.0 1
Vascular endothelial growth factor receptor 3
CHEMBL1955
Ki 8.1 8.1 8.0 1
Mitogen-activated protein kinase kinase kinase 9
CHEMBL2872
Ki 7.82 7.82 15.0 1
Receptor-type tyrosine-protein kinase FLT3
CHEMBL1974
Ki 7.75 7.32 18.0 2
HT-29
CHEMBL384
IC50 7.72 7.72 19.0 1
Dual specificity tyrosine-phosphorylation-regulated kinase 2
CHEMBL4376
Ki 7.58 7.58 26.0 1
Tyrosine-protein kinase Mer
CHEMBL5331
Ki 7.52 7.52 30.0 1
Glycogen synthase kinase-3 alpha
CHEMBL2850
Ki 7.48 7.48 33.0 1
Mast/stem cell growth factor receptor Kit
CHEMBL1936
Ki 7.41 7.41 39.0 1
Serine-protein kinase ATM
CHEMBL3797
Ki 7.36 7.36 44.0 1
Tyrosine-protein kinase ABL1
CHEMBL1862
Ki 7.23 7.23 59.0 1
Serine-protein kinase ATM
CHEMBL3797
IC50 7.07 7.07 85.0 1
Glycogen synthase kinase-3 beta
CHEMBL262
Ki 6.85 6.85 140.0 1
PI3-kinase p110-alpha/p85-alpha
CHEMBL2111367
Ki 6.85 6.85 140.0 1
Tyrosine-protein kinase JAK2
CHEMBL2971
Ki 6.82 6.82 150.0 1
Tyrosine-protein kinase SYK
CHEMBL2599
Ki 6.72 6.72 190.0 1
Phosphatidylinositol 3-kinase regulatory subunit alpha
CHEMBL2506
IC50 6.12 6.12 750.0 1
Voltage-gated inwardly rectifying potassium channel KCNH2
CHEMBL240
IC50 5.52 5.52 3000.0 1
DNA-dependent protein kinase catalytic subunit
CHEMBL3142
IC50 5.44 5.44 3600.0 1
Serine/threonine-protein kinase mTOR
CHEMBL2842
IC50 5.32 5.32 4800.0 1

Pharmacokinetic Data

Parameter Value Units Species
CL 26.0 mL.min-1.kg-1 Rattus norvegicus
T1/2 11.6 hr Rattus norvegicus

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Serine/threonine-protein kinase ATR Ki = 0.148 nM 9.83 ATR Inhibition Assay: Compounds can be screened for their ability to inhibit ATR... -
Serine/threonine-protein kinase ATR Ki = 0.148 nM 9.83 Inhibition Assay: Compounds can be screened for their ability to inhibit ATR kin... -
Serine/threonine-protein kinase ATR Ki = 0.165 nM 9.78 Inhibition of recombinant human full-length N-terminal Flag epitope-tagged ATR e... 31074988
Serine/threonine-protein kinase ATR IC50 = 0.17 nM 9.77 Inhibition of ATR (unknown origin) 38325007
Alpha-1-antitrypsin-related protein IC50 = 0.2 nM 9.7 Binding affinity to ATR (unknown origin) 33970631
Serine/threonine-protein kinase ATR Ki = 0.2 nM 9.7 ATR Inhibition Assay: Compounds can be screened for their ability to inhibit ATR... -
Serine/threonine-protein kinase ATR Ki = 0.2 nM 9.7 Inhibition Assay: Compounds can be screened for their ability to inhibit ATR kin... -
SARS-CoV-2 IC50 = 4.28 nM 8.37 Antiviral activity against SARS-CoV-2 in 1 to 24 hrs pretreated cells measured a... 33539089
SARS-CoV-2 IC50 = 4.28 nM 8.37 Antiviral activity against SARSCoV-2 33539089
Unchecked IC50 = 5.0 nM 8.3 Inhibition of human full length recombinant ATR M211T mutant using GST-c-Myc-p53... 38299539
Vascular endothelial growth factor receptor 3 Ki = 8.0 nM 8.1 ATP competitive inhibition of human Flt4 31074988
Serine/threonine-protein kinase ATR IC50 = 9.0 nM 8.05 Inhibition of human recombinant full length ATR using GST-cMyc-p53 as substrate ... 35183872
Serine/threonine-protein kinase ATR IC50 = 15.0 nM 7.82 Inhibition of human recombinant FLAG-tagged full length ATR expressed in mammali... 28131712
Mitogen-activated protein kinase kinase kinase 9 Ki = 15.0 nM 7.82 ATP competitive inhibition of human MLK1 31074988
Receptor-type tyrosine-protein kinase FLT3 Ki = 18.0 nM 7.75 ATP competitive inhibition of human Flt3 D835Y mutant 31074988
Serine/threonine-protein kinase ATR IC50 = 19.0 nM 7.72 Inhibition of ATR in human HCT116 cells assessed as reduction in histone H2AX ph... 31074988
Serine/threonine-protein kinase ATR IC50 = 19.0 nM 7.72 Inhibition of ATR (unknown origin) 33539089
HT-29 IC50 = 19.0 nM 7.72 Antiproliferative activity against human HT-29 cells assessed as reduction in ce... 37300915
Dual specificity tyrosine-phosphorylation-regulated kinase 2 Ki = 26.0 nM 7.58 ATP competitive inhibition of human DYRK2 31074988
Tyrosine-protein kinase Mer Ki = 30.0 nM 7.52 ATP competitive inhibition of human Mer 31074988

Literature References

Data from ChEMBL 36 via Core Engine